SRY IS A TRANSCRIPTIONAL ACTIVATOR
SRY IS A TRANSCRIPTIONAL ACTIVATOR
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DOI：
10.1210/me.8.9.1182
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发表时间：
1994-09-01
影响因子：
--
通讯作者：
OSTRER, H
中科院分区：
文献类型：
--
作者：
DUBIN, RA;OSTRER, H
SRY基因在性腺嵴启动睾丸决定中起着遗传开关的作用。小鼠SRY和人SRY开放阅读框（ORF）共享保守的DNA结合结构域（HMG盒），但在该区域之外没有表现出额外的同源性。根据lacZ-SRY杂合蛋白在细胞核中的积累判断，人和小鼠SRY ORF都含有核定位信号。当用随机寡核苷酸池攻击时，小鼠Sry HMG盒结构域在体外选择性结合序列NACAAT，并以最高亲和力结合AACAAT。当置于异源启动子的控制下时，小鼠Sry基因激活含有AACAAT结合位点的多个拷贝的报告基因的转录。当小鼠Sry基因与GAL 4的DNA结合结构域连接时，同样观察到GAL 4应答报告基因的激活。使用这个系统，激活功能被映射到一个谷氨酰胺/组氨酸丰富的结构域。此外，LexA-小鼠Sry融合基因激活酵母中的LexA应答报告基因。相反，GAL 4-人SRY融合基因不引起转录激活。这些研究表明，人类和小鼠SRY ORF编码核，DNA结合蛋白和小鼠Sry ORF可以作为一个转录激活因子与分离的DNA结合和激活域。
The SRY gene functions as a genetic switch in gonadal ridge initiating testis determination. The mouse Sry and human SRY open reading frames (ORFs) share a conserved DNA-binding domain (the HMG-box) yet exhibit no additional homology outside this region. As judged by the accumulation of lacZ-SRY hybrid proteins in the nucleus, both the human and mouse SRY ORFs contain a nuclear localization signal. The mouse Sry HMG-box domain selectively binds the sequence NACAAT in vitro when challenged with a random pool of oligonucleotides and binds AACAAT with the highest affinity. When put under the control of a heterologous promotor, the mouse Sry gene activated transcription of a reporter gene containing multiple copies of the AACAAT binding site. Activation was likewise observed for a GAL4-responsive reporter gene, when the mouse Sry gene was linked to the DNA-binding domain of GAL4. Using this system, the activation function was mapped to a glutamine/histidine-rich domain. In addition, LexA-mouse Sry fusion genes activated a LexA-responsive reporter gene in yeast. In contrast, a GAL4-human SRY fusion gene did not cause transcriptional activation. These studies suggest that both the human and the mouse SRY ORFs encode nuclear, DNA-binding proteins and that the mouse Sry ORF can function as a transcriptional activator with separable DNA-binding and activator domains.